Heat-related changes in the velocity and kinetic energy of flowing blood influence the human heart's output during hyperthermia.

Passive whole-body hyperthermia increases limb blood flow and cardiac output ( Q ̇ $\dot Q$ ), but the interplay between peripheral and central thermo-haemodynamic mechanisms remains unclear. Here we tested the hypothesis that local hyperthermia-induced alterations in peripheral blood flow and blood kinetic energy modulate flow to the heart and Q ̇ $\dot Q$ . Body temperatures, regional (leg, arm, head) and systemic haemodynamics, and left ventricular (LV) volumes and functions were assessed in eight healthy males during: (1) 3 h control (normothermic condition); (2) 3 h of single-leg heating; (3) 3 h of two-leg heating; and (4) 2.5 h of whole-body heating. Leg, forearm, and extracranial blood flow increased in close association with local rises in temperature while brain perfusion remained unchanged. Increases in blood velocity with small to no changes in the conduit artery diameter underpinned the augmented limb and extracranial perfusion. In all heating conditions, Q ̇ $\dot Q$ increased in association with proportional elevations in systemic vascular conductance, related to enhanced blood flow, blood velocity, vascular conductance and kinetic energy in the limbs and head (all R2 ≥ 0.803; P < 0.001), but not in the brain. LV systolic (end-systolic elastance and twist) and diastolic functional profiles (untwisting rate), pulmonary ventilation and systemic aerobic metabolism were only altered in whole-body heating. These findings substantiate the idea that local hyperthermia-induced selective alterations in peripheral blood flow modulate the magnitude of flow to the heart and Q ̇ $\dot Q$ through changes in blood velocity and kinetic energy. Localised heat-activated events in the peripheral circulation therefore affect the human heart's output. KEY POINTS: Local and whole-body hyperthermia increases limb and systemic perfusion, but the underlying peripheral and central heat-sensitive mechanisms are not fully established. Here we investigated the regional (leg, arm and head) and systemic haemodynamics (cardiac output: Q ̇ $\dot Q$ ) during passive single-leg, two-leg and whole-body hyperthermia to determine the contribution of peripheral and central thermosensitive factors in the control of human circulation. Single-leg, two-leg, and whole-body hyperthermia induced graded increases in leg blood flow and Q ̇ $\dot Q$ . Brain blood flow, however, remained unchanged in all conditions. Ventilation, extracranial blood flow and cardiac systolic and diastolic functions only increased during whole-body hyperthermia. The augmented Q ̇ $\dot Q$ with hyperthermia was tightly related to increased limb and head blood velocity, flow and kinetic energy. The findings indicate that local thermosensitive mechanisms modulate regional blood velocity, flow and kinetic energy, thereby controlling the magnitude of flow to the heart and thus the coupling of peripheral and central circulation during hyperthermia.

Blood flow kinetic energy is a novel marker for right ventricular global systolic function in patients with left ventricular assist device therapy.

Objectives: Right ventricular (RV) failure remains a major concern in heart failure (HF) patients undergoing left ventricular assist device (LVAD) implantation. We aimed to measure the kinetic energy of blood in the RV outflow tract (KE-RVOT) - a new marker of RV global systolic function. We also aimed to assess the relationship of KE-RVOT to other echocardiographic parameters in all subjects and assess the relationship of KE-RVOT to hemodynamic parameters of RV performance in HF patients. Methods: Fifty-one subjects were prospectively enrolled into 4 groups (healthy controls, NYHA Class II, NYHA Class IV, LVAD patients) as follows: 11 healthy controls, 32 HF patients (8 NYHA Class II and 24 Class IV), and 8 patients with preexisting LVADs. The 24 Class IV HF patients included 21 pre-LVAD and 3 pre-transplant patients. Echocardiographic parameters of RV function (TAPSE, St', Et', IVA, MPI) and RV outflow color-Doppler images were recorded in all patients. Invasive hemodynamic parameters of RV function were collected in all Class IV HF patients. KE-RVOT was derived from color-Doppler imaging using a vector flow mapping proprietary software. Kruskal-Wallis test was performed for comparison of KE-RVOT in each group. Correlation between KE-RVOT and echocardiographic/hemodynamic parameters was assessed by linear regression analysis. Receiver operating characteristic curves for the ability of KE-RVOT to predict early phase RV failure were generated. Results: KE-RVOT (median ± IQR) was higher in healthy controls (55.10 [39.70 to 76.43] mW/m) than in the Class II HF group (22.23 [15.41 to 35.58] mW/m, p < 0.005). KE-RVOT was further reduced in the Class IV HF group (9.02 [5.33 to 11.94] mW/m, p < 0.05). KE-RVOT was lower in the LVAD group (25.03 [9.88 to 38.98] mW/m) than the healthy controls group (p < 0.005). KE-RVOT had significant correlation with all echocardiographic parameters and no correlation with invasive hemodynamic parameters. RV failure occurred in 12 patients who underwent LVAD implantation in the Class IV HF group (1 patient was not eligible due to death immediately after the LVAD implantation). KE-RVOT cut-off value for prediction of RV failure was 9.15 mW/m (sensitivity: 0.67, specificity: 0.75, AUC: 0.66). Conclusions: KE-RVOT, a novel noninvasive measure of RV function, strongly correlates with well-established echocardiographic markers of RV performance. KE-RVOT is the energy generated by RV wall contraction. Therefore, KE-RVOT may reflect global RV function. The utility of KE-RVOT in prediction of RV failure post LVAD implantation requires further study.

Time-trend analysis of the center frequency of the intrinsic mode function from the Hilbert-Huang transform of electroencephalography during general anesthesia: a retrospective observational study.

BACKGROUND: Anesthesiologists are required to maintain an optimal depth of anesthesia during general anesthesia, and several electroencephalogram (EEG) processing methods have been developed and approved for clinical use to evaluate anesthesia depth. Recently, the Hilbert-Huang transform (HHT) was introduced to analyze nonlinear and nonstationary data. In this study, we assessed whether the changes in EEG characteristics during general anesthesia that are analyzed by the HHT are useful for monitoring the depth of anesthesia. METHODS: This retrospective observational study enrolled patients who underwent propofol anesthesia. Raw EEG signals were obtained from a monitor through a previously developed software application. We developed an HHT analyzer to decompose the EEG signal into six intrinsic mode functions (IMFs) and estimated the instantaneous frequencies (HHT_IF) for each IMF. Changes over time in the raw EEG waves and parameters such as HHT_IF, BIS, spectral edge frequency 95 (SEF95), and electromyogram parameter (EMGlow) were assessed, and a Gaussian process regression model was created to assess the association between BIS and HHT_IF. RESULTS: We analyzed EEG signals from 30 patients. The beta oscillation frequency range (13-25 Hz) was detected in IMF1 and IMF2 during the awake state, then after loss of consciousness, the frequency decreased and alpha oscillation (8-12 Hz) was detected in IMF2. At the emergence phase, the frequency increased and beta oscillations were detected in IMF1, IMF2, and IMF3. BIS and EMGlow changed significantly during the induction and emergence phases, whereas SEF95 showed a wide variability and no significant changes during the induction phase. The root mean square error between the observed BIS values and the values predicted by a Gaussian process regression model ranged from 4.69 to 9.68. CONCLUSIONS: We applied the HHT to EEG analyses during propofol anesthesia. The instantaneous frequency in IMF1 and IMF2 identified changes in EEG characteristics during induction and emergence from general anesthesia. Moreover, the HHT_IF in IMF2 showed strong associations with BIS and was suitable for depicting the alpha oscillation. Our study suggests that the HHT is useful for monitoring the depth of anesthesia.

Pulsatility and flow patterns across macro- and microcirculatory arteries of continuous-flow left ventricular assist device patients.

BACKGROUND: Reduced arterial pulsatility in continuous-flow left ventricular assist devices (CF-LVAD) patients has been implicated in clinical complications. Consequently, recent improvements in clinical outcomes have been attributed to the "artificial pulse" technology inherent to the HeartMate3 (HM3) LVAD. However, the effect of the "artificial pulse" on arterial flow, transmission of pulsatility into the microcirculation and its association with LVAD pump parameters is not known. METHODS: The local flow oscillation (pulsatility index, PI) of common carotid arteries (CCAs), middle cerebral arteries (MCAs) and central retinal arteries (CRAs-representing the microcirculation) were quantified by 2D-aligned, angle-corrected Doppler ultrasound in 148 participants: healthy controls, n = 32; heart failure (HF), n = 43; HeartMate II (HMII), n = 32; HM3, n = 41. RESULTS: In HM3 patients, 2D-Doppler PI in beats with "artificial pulse" and beats with "continuous-flow" was similar to that of HMII patients across the macro- and microcirculation. Additionally, peak systolic velocity did not differ between HM3 and HMII patients. Transmission of PI into the microcirculation was higher in both HM3 (during the beats with "artificial pulse") and in HMII patients compared with HF patients. LVAD pump speed was inversely associated with microvascular PI in HMII and HM3 (HMII, r2 = 0.51, p < 0.0001; HM3 "continuous-flow," r2 = 0.32, p = 0.0009; HM3 "artificial pulse," r2 = 0.23, p = 0.007), while LVAD pump PI was only associated with microcirculatory PI in HMII patients. CONCLUSIONS: The "artificial pulse" of the HM3 is detectable in the macro- and microcirculation but without creating a significant alteration in PI compared with HMII patients. Increased transmission of pulsatility and the association between pump speed and PI in the microcirculation indicate that the future clinical care of HM3 patients may involve individualized pump settings according to the microcirculatory PI in specific end-organs.

Regiospecific and Enantiospecific Effects of the ß-Benzyl-α-benzylidene-γ-butyrolactone Structure on Phytotoxic Fungi.

Novel derivatives of E-ß-benzyl-α-benzylidene-γ-butyrolactone (3-benzyl-2-benzylidene-4-butanolide) with lignano-9,9'-lactone structures were developed as anti-phytopathogenic fungal compounds. Their regiospecific and enantiospecific characteristics were determined, with the E-form and 3R-configuration showing higher activities against the Alternaria alternata Japanese pear pathotype. By the syntheses of benzyl compounds instead of benzylidene and aromatic derivatives, followed by an bioassay experiment, the importance of the benzylidene structure and effects of the substituents of the aromatic ring were clarified. The (2-OCH3, 4'-CH3/4'-CF3)-derivatives, 19 and 25, and (2-OCH3, 6-CH3/6-F/6-Br, 4'-OCH3)-derivatives, 34, 38, and 42, were more effective with EC50 values of 0.1-0.3 µM. It was assumed that the 2-OCH3 group, a hydrophobic group at the 6-position, and some size of the hydrophobic group at the 4'-position were necessary for the increased activity.

Correlation between aortic valve protein levels and vector flow mapping of wall shear stress and oscillatory shear index in patients supported with continuous-flow left ventricular assist devices.

BACKGROUND: Continuous-flow left ventricular assist devices commonly lead to aortic regurgitation, which results in decreased pump efficiency and worsening heart failure. We hypothesized that non-physiological wall shear stress and oscillatory shear index alter the abundance of structural proteins in aortic valves of left ventricular assist device (LVAD) patients. METHODS: Doppler images of aortic valves of patients undergoing heart transplants were obtained. Eight patients had been supported with LVADs, whereas 10 were not. Aortic valve tissue was collected and protein levels were analyzed using mass spectrometry. Echocardiographic images were analyzed and wall shear stress and oscillatory shear index were calculated. The relationship between normalized levels of individual proteins and in vivo echocardiographic measurements was evaluated. RESULTS: Of the 57 proteins of interest, there was a strong negative correlation between levels of 15 proteins and the wall shear stress (R < -0.500, p ≤ 0.05), and a moderate negative correlation between 16 proteins and wall shear stress (R -0.500 to -0.300, p ≤ 0.05). Gene ontology analysis demonstrated clusters of proteins involved in cellular structure. Proteins negatively correlated with WSS included those with cytoskeletal, actin/myosin, cell-cell junction and extracellular functions. C: In aortic valve tissue, 31 proteins were identified involved in cellular structure and extracellular junctions with a negative correlation between their levels and wall shear stress. These findings suggest an association between the forces acting on the aortic valve (AV) and leaflet protein abundance, and may form a mechanical basis for the increased risk of aortic leaflet degeneration in LVAD patients.

A vacuolar membrane protein Vsb1p contributes to the vacuolar compartmentalization of basic amino acids in Schizosaccharomyces pombe.

Accumulation levels of Arg, Lys, and His in vacuoles of Schizosaccharomyces pombe cells were drastically decreased by the disruption of SPAC24H6.11c (vsb1+) gene identified by a homology search with the VSB1 gene of Saccharomyces cerevisiae. The Vsb1p fused with green fluorescent protein particularly localized at vacuolar membranes in S. pombe cells. Overexpression of vsb1+ markedly increased vacuolar levels of basic amino acids; however, overexpression of the vsb1D174A mutant did not affect the levels of these amino acids. These results suggest that the vsb1+ contributes to the accumulation of basic amino acids into the vacuoles of S. pombe, and the aspartate residue in the putative first transmembrane domain conserved among fungal homologs is crucial for the function of Vsb1p.

Preoperative Left Ventricular Energy Loss in the Operating Theater Reflects Subjective Symptoms in Chronic Aortic Regurgitation.

BACKGROUND: There is currently no subjective, definitive evaluation method for therapeutic indication other than symptoms in aortic regurgitation. Energy loss, a novel parameter of cardiac workload, can be visualized and quantified using echocardiography vector flow mapping. The purpose of the present study was to evaluate whether energy loss in patients with chronic aortic regurgitation can quantify their subjective symptoms more clearly than other conventional metrics. METHODS: We studied 15 patients undergoing elective aortic valve surgery for aortic regurgitation. We divided the patients into symptomatic and asymptomatic groups using their admission records. We analyzed the mean energy loss in one cardiac cycle using transesophageal echocardiography during the preoperative period. The relationships between symptoms, energy loss, and other conventional metrics were statistically analyzed. RESULTS: There were seven and eight patients in the symptomatic and asymptomatic groups, respectively. The mean energy loss of one cardiac cycle was higher in the symptomatic group (121 mW/m [96-184]) than in the asymptomatic group (87 mW/m [80-103]) (p = 0.040), whereas the diastolic diameter was higher in the asymptomatic group (65 mm [59-78]) than in the symptomatic group (57 mm [51-57]) (p = 0.040). There was no significant difference between the symptomatic and asymptomatic groups in terms of other conventional metrics. CONCLUSIONS: An energy loss can quantify patients' subjective symptoms more clearly than other conventional metrics. The small sample size is the primary limitation of our study, further studies assessing larger cohort of patients are warranted to validate our findings.

Left Ventricular Assist Device Support-Induced Alteration of Mechanical Stress on Aortic Valve and Aortic Wall.

The aim of this study was to evaluate the fluid dynamics in the aortic valve and proximal aorta during continuous-flow left ventricular assist device (LVAD) support using epiaortic echocardiography and vector flow mapping technology. A total of 12 patients who underwent HeartMate 3 implantation between December 2018 and February 2020 were prospectively examined. The wall shear stress (WSS) on the ascending aorta, aortic root, and aortic valve was evaluated before and after LVAD implantation. The median age of the cohort was 62 years and 17% were women. The peak WSS on the ascending aorta (Pre 1.48 [0.86-1.69] [Pascal {Pa}] vs. Post 0.33 [0.21-0.58] [Pa]; p = 0.002), aortic root (Pre 0.46 [0.31-0.58] (Pa) vs. Post 0.18 [0.12-0.25] (Pa); p = 0.001), and ventricularis of the aortic valve (Pre 1.76 [1.59-2.30] (Pa) vs. Post 0.30 [0.10-0.61] (Pa); p = 0.001) was significantly lower after LVAD implantation. No difference in WSS was observed on the fibrosa of the aortic valve (Pre 0.36 [0.22-0.53] (Pa) vs. Post 0.38 [0.38-0.52] (Pa); p = 0.850) before and after implantation. The WSS on the ascending aorta, aortic root, and ventricularis of the aortic valve leaflets was significantly altered by LVAD implantation, providing preliminary data on the potential contribution of fluid dynamics to LVAD-induced aortic insufficiency and root thrombus.

Cerebral vasoreactivity in HeartMate 3 patients.

BACKGROUND: While rates of stroke have declined with the HeartMate3 (HM3) continuous- flow (CF) left ventricular assist device (LVAD), the impact of non-pulsatile flow and artificial pulse physiology on cerebrovascular function is not known. We hypothesized that improved hemodynamics and artificial pulse physiology of HM3 patients would augment cerebrovascular metabolic reactivity (CVR) compared with HeartMate II (HMII) CF-LVAD and heart failure (HF) patients. METHODS: Mean, peak systolic and diastolic flow velocities (MFV, PSV, MinFV, respectively) and cerebral pulsatility index were determined in the middle cerebral artery (MCA) before and after a 30 sec breath-hold challenge in 90 participants: 24 healthy controls; 30 HF, 15 HMII, and 21 HM3 patients. RESULTS: In HM3 patients, breath-holding increased MFV (Δ8 ± 10 cm/sec, p < .0001 vs baseline) to levels similar to HF patients (Δ9 ± 8 cm/sec, p > .05), higher than HMII patients (Δ2 ± 8 cm/sec, p < .01) but lower than healthy controls (Δ13 ± 7 cm/sec, p < .05). CF-LVAD altered the proportion of systolic and diastolic flow responses as reflected by a differential cerebral pulsatility index (p = .03). Baseline MFV was not related to CVR (r2 = 0.0008, p = .81). However, CF-LVAD pump speed was strongly inversely associated with CVR in HM II (r2 = 0.51, p = .003) but not HM3 patients (r2 = 0.01, p = .65). CONCLUSIONS: Compared with HMII, HM3 patients have a significantly improved CVR. However, CVR remains lower in HM3 and HF patients than in healthy controls, therefore suggesting that changes in cerebral hemodynamics are not reversed by CF-LVAD therapy. Further research on the mechanisms and the long-term impact of altered cerebral hemodynamics in this unique patient population are warranted.

Difficult Airway Management in Neonates and Infants: Knowledge of Devices and a Device-Oriented Strategy.

Difficult airway management (DAM) in neonates and infants requires anesthesiologists and critical care clinicians to respond rapidly with appropriate evaluation of specific situations. Therefore, organizing information regarding DAM devices and device-oriented guidance for neonate and infant DAM treatment will help practitioners select the safest and most effective strategy. Based on DAM device information and reported literature, there are three modern options for DAM in neonates and infants that can be selected according to the anatomical difficulty and device-oriented strategy: (1) video laryngoscope (VLS), (2) supraglottic airway device (SAD), and (3) flexible fiberoptic scope (FOS). Some VLSs are equipped with small blades for infants. Advanced SADs have small sizes for infants, and some effectively function as conduits for endotracheal intubation. The smallest FOS has an outer diameter of 2.2 mm and enables intubation with endotracheal tubes with an inner diameter of 3.0 mm. DAM in neonates and infants can be improved by effectively selecting the appropriate device combination and ensuring that available providers have the necessary skills.

Influence of aneurysmal aortic root geometry on mechanical stress to the aortic valve leaflet.

AIMS: While mechanical stress caused by blood flow, e.g. wall shear stress (WSS), and related parameters, e.g. oscillatory shear index (OSI), are increasingly being recognized as key moderators of various cardiovascular diseases, studies on valves have been limited because of a lack of appropriate imaging modalities. We investigated the influence of aortic root geometry on WSS and OSI on the aortic valve (AV) leaflet. METHODS AND RESULTS: We applied our novel approach of intraoperative epi-aortic echocardiogram to measure the haemodynamic parameters of WSS and OSI on the AV leaflet. Thirty-six patients were included, which included those who underwent valve-sparing aortic root replacement (VSARR) with no significant aortic regurgitation (n = 17) and coronary artery bypass graft (CABG) with normal AV (n = 19). At baseline, those who underwent VSARR had a higher systolic WSS (0.52 ± 0.12 vs. 0.32 ± 0.08 Pa, respectively, P < 0.001) and a higher OSI (0.37 ± 0.06 vs. 0.29 ± 0.04, respectively, P < 0.001) on the aortic side of the AV leaflet than those who underwent CABG. Multivariate regression analysis revealed that the size of the sinus of Valsalva had a significant association with WSS and OSI. Following VSARR, WSS and OSI values decreased significantly compared with the baseline values (WSS: 0.29 ± 0.12 Pa, P < 0.001; OSI: 0.26 ± 0.09, P < 0.001), and became comparable to the values in those who underwent CABG (WSS, P = 0.42; OSI, P = 0.15). CONCLUSIONS: Mechanical stress on the AV gets altered in correlation with the size of the aortic root. An aneurysmal aortic root may expose the leaflet to abnormal fluid dynamics. The VSARR procedure appeared to reduce these abnormalities.

Poincaré Plot Area of Gamma-Band EEG as a Measure of Emergence From Inhalational General Anesthesia.

The Poincaré plot obtained from electroencephalography (EEG) has been used to evaluate the depth of anesthesia. A standalone EEG Analyzer application was developed; raw EEG signals obtained from a bispectral index (BIS) monitor were analyzed using an on-line monitoring system. Correlations between Poincaré plot parameters and other measurements associated with anesthesia depth were evaluated during emergence from inhalational general anesthesia. Of the participants, 20 were adults anesthetized with sevoflurane (adult_S E V ), 20 were adults anesthetized with desflurane (adult_D E S ), and 20 were pediatric patients anesthetized with sevoflurane (ped_S E V ). EEG signals were preprocessed through six bandpass digital filters (f0: 0.5-47 Hz, f1: 0.5-8 Hz, f2: 8-13 Hz, f3: 13-20 Hz, f4: 20-30 Hz, and f5: 30-47 Hz). The Poincaré plot-area ratio (PPAR = PP A_fx /PP A_f0 , fx = f1∼f5) was analyzed at five frequency ranges. Regardless of the inhalational anesthetic used, there were strong linear correlations between the logarithm of PP AR at f5 and BIS (R 2 = 0.67, 0.79, and 0.71, in the adult_S E V , adult_D E S , and ped_S E V groups, respectively). As an additional observation, a part of EMG activity at the gamma range of 30-47 Hz probably influenced the calculations of BIS and PP AR_f5 with a non-negligible level. The logarithm of PPAR in the gamma band was most sensitive to state changes during the emergence process and could provide a new non-proprietary parameter that correlates with changes in BIS during measurement of anesthesia depth.

Intraoperative Diagnosis of a Stuck Bioprosthetic Valve Leaflet Due to a Loop of Suture After Mitral Valve Replacement.

A stuck mechanical valve leaflet is a well-known cardiovascular complication; however, a stuck bioprosthetic valve is a rare but potentially fatal complication. Herein a case of stuck bioprosthetic mitral valve caused by a loop of suture, which was detected on intraoperative 3-dimensional (3D) transesophageal echocardiography immediately after cardiopulmonary bypass, is presented. Restricted motion of the 2 leaflets during diastole and incomplete coaptation during systole were observed clearly on 3D imaging. Thus, intraoperative 3D transesophageal echocardiography imaging is useful for detecting such complications immediately after cardiopulmonary bypass.

Dehydration reduces stroke volume and cardiac output during exercise because of impaired cardiac filling and venous return, not left ventricular function.

Dehydration accrued during intense prolonged whole-body exercise in the heat compromises peripheral blood flow and cardiac output ( Q˙ ). A markedly reduced stroke volume (SV) is a key feature of the dehydration-induced cardiovascular strain, but whether the lower output of the heart is mediated by peripheral or cardiac factors remains unknown. Therefore, we repeatedly quantified left ventricular (LV) volumes, LV mechanics (LV twist, a marker of systolic muscle function, and LV untwisting rate, an independent marker of LV muscle relaxation), left intra-ventricular pressure gradients, blood volume and peripheral blood flow during 2 hr of cycling in the heat with and without dehydration (DEH: 4.0 ± 0.2% body mass loss and EUH: euhydration control, respectively) in eight participants (three females and five males). While brachial and carotid blood flow, blood volume, SV, LV end-diastolic volume (LVEDV), cardiac filling time, systemic vascular conductance and Q˙ were reduced in DEH compared to EUH after 2 hr, LV twist and untwisting rate tended to be higher (p = .09 and .06, respectively) and intra-ventricular pressure gradients were not different between the two conditions (p = .22). Furthermore, LVEDV in DEH correlated strongly with blood volume (r = .995, p < .01), head and forearms beat volume (r = .98, p < .05), and diastolic LV filling time (r = .98, p < .05). These findings suggest that the decline in SV underpinning the blunted Q˙ with exercise-induced dehydration is caused by compromised LV filling and venous return, but not intrinsic systolic or diastolic LV function.